Evidence map›Paper›PMID 40707596›Full record

ArticleScientific reports2025

Single-cell RNA sequencing analysis revealed the immunosuppressive remodeling of tumor-associated macrophages mediated by the MIF-CD74 axis in gastric cancer.

Weiwei Liu, Chuangyuan Wang, Lixin Liang, Congcong Zhang, Yanyan Li, Jun Xiao, Rui Zeng, Jingyu Li, Zhihao Lin, Qinghua Huang and 2 more

Abstract read
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed.

  1. Review
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  4. A POSTNInternational journal of general medicine · 2026
    Article
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  7. CLEVER-1Frontiers in immunology · 2026
    Review
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  11. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Weiwei Liu *Department of Pathology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, Guangdong, China.
Chuangyuan Wang *The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
Lixin Liang *Department of Oral Pathology, Guangdong Provincial Key Laboratory of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China.
Congcong ZhangGuangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
Yanyan LiGuangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
Jun XiaoDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Rui ZengGuangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
Jingyu LiDepartment of Pathology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, Guangdong, China.
Zhihao LinGuangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
Qinghua HuangDepartment of Pathology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, Guangdong, China.
Lisheng ZhengDepartment of Pathology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, Guangdong, China. zhenglisheng@gdph.org.cn.
Qingling ZhangDepartment of Pathology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, Guangdong, China. zhangqingling@gdph.org.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tumor-associated macrophages (TAMs) are pivotal immunosuppressive components of the tumor microenvironment (TME) in gastric cancer (GC), yet their heterogeneity and metabolic crosstalk with tumor cells remain poorly understood. Here, we performed single-cell RNA sequencing (scRNA-seq) on 75,743 cells from 11 GC tissues and identified four distinct TAM subsets (TAM-APOE, TAM-IDO1, TAM-SKAP1, TAM-POLB), each exhibiting unique functional signatures. Among these, the TAM-APOE subset, enriched in lipid metabolism and complement pathways, showed the strongest interaction with tumor cells via the MIF-CD74 axis. Functional studies revealed that GC-derived MIF promotes TAM-APOE polarization, upregulating immunosuppressive genes and enhancing tumor progression. In vivo, MIF overexpression in GC cells increases subcutaneous tumor volume, while MIF knockdown decreases tumor weight. Crucially, Milatuzumab, a CD74-targeting antibody, reversed MIF-induced TAM immunosuppression in vitro. Our research provides a comprehensive map of GC-TAM heterogeneity; reveals that the MIF-CD74 axis is a key driver of TAM-mediated immune suppression; and proposes that CD74 blockade is a new therapeutic strategy for GC.

Indexed as

Antigens, Differentiation, B-LymphocyteHistocompatibility Antigens Class IIIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsStomach NeoplasmsTumor-Associated MacrophagesAnimalsCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansMaleMiceSequence Analysis, RNASingle-Cell AnalysisTumor MicroenvironmentAntigens, Differentiation, B-LymphocyteHistocompatibility Antigens Class IIIntramolecular Oxidoreductasesinvariant chainMacrophage Migration-Inhibitory FactorsMIF protein, humanGastric cancerImmunotherapyMIF-CD74 axisSingle-cell RNA sequencingTumor-associated macrophages

Identifiers

PMID40707596
PMCPMC12290046

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.